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Frontiers in Endocrinology 2022To perform a systematic review and meta-analysis of interferon and endocrine side effects, including their incidence, evaluation, and management. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To perform a systematic review and meta-analysis of interferon and endocrine side effects, including their incidence, evaluation, and management.
METHODS
PubMed was searched through March 7th, 2021, by 2 authors independently (LH Wang and H Zhao). Early phase I/II, phase III experimental trials, prospective and retrospective observational studies were included. Stata 16.0 (StataCorp LLC, 16.0) was the main statistical software for meta-analysis. The weighted incidence and risk ratio were estimated for primary thyroid disease and diabetes mellitus.
RESULTS
A total of 108 studies involving 46265 patients were included. Hypothyroidism was the most common thyroid disorder, followed by hyperthyroidism. IFN α+RBV treated patients experienced hypothyroidism in 7.8% (95%CI, 5.9-9.9), which was higher than IFN α (5.2%; 95%CI, 3.7-6.8) and IFN β (7.0%; 95%CI, 0.06-23.92). IFN α+RBV treated patients experienced hyperthyroidism in 5.0% (95%CI, 3.6-6.5), which was higher than IFN α (3.5%; 95%CI, 2.5-4.8) and IFN β (3.4%; 95%CI, 0.9-7.5). The summary estimated incidence of painless thyroiditis was 5.8% (95%CI, 2.8-9.8) for IFN α, and 3.5% (95%CI,1.9-5.5) for IFN α+RBV. The summary estimated incidence of diabetes was 1.4% (95%CI, 0.3-3.1) for IFN, 0.55% (95%CI, 0.05-1.57) for IFN α, 3.3% (95%CI,1.1-6.6) for IFN α+RBV.
CONCLUSIONS
Our meta-analysis shows a high incidence of endocrine adverse events provoked by IFN, further reinforced by combined RBV treatment.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42022334131.
Topics: Antiviral Agents; Humans; Hyperthyroidism; Hypothyroidism; Interferon-alpha; Prospective Studies; Retrospective Studies; Thyroid Diseases
PubMed: 35992107
DOI: 10.3389/fendo.2022.949003 -
Journal of Microbiology, Immunology,... Oct 2021Despite aggressive efforts on containment measures for the coronavirus disease 2019 (COVID-19) pandemic around the world, severe acute respiratory syndrome coronavirus 2... (Review)
Review
Despite aggressive efforts on containment measures for the coronavirus disease 2019 (COVID-19) pandemic around the world, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously spreading. Therefore, there is an urgent need for an effective antiviral agent. To date, considerable research has been conducted to develop different approaches to COVID-19 therapy. In addition to early observational studies, which could be limited by study design, small sample size, non-randomized design, or different timings of treatment, an increasing number of randomized controlled trials (RCTs) investigating the clinical efficacy and safety of antiviral agents are being carried out. This study reviews the updated findings of RCTs regarding the clinical efficacy of eight antiviral agents against COVID-19, including remdesivir, lopinavir/ritonavir, favipiravir, sofosbuvir/daclatasvir, sofosbuvir/ledipasvir, baloxavir, umifenovir, darunavir/cobicistat, and their combinations. Treatment with remdesivir could accelerate clinical improvement; however, it lacked additional survival benefits. Moreover, 5-day regimen of remdesivir might show adequate effectiveness in patients with mild to moderate COVID-19. Favipiravir was only marginally effective regarding clinical improvement and virological assessment based on the results of small RCTs. The present evidence suggests that sofosbuvir/daclatasvir may improve survival and clinical outcomes in patients with COVID-19. However, the sample sizes for analysis were relatively small, and all studies were exclusively conducted in Iran. Further larger RCTs in other countries are warranted to support these findings. In contrast, the present findings of limited RCTs did not indicate the use of lopinavir/ritonavir, sofosbuvir/ledipasvir, baloxavir, umifenovir, and darunavir/cobicistat in the treatment of patients hospitalized for COVID-19.
Topics: Adenosine Monophosphate; Alanine; Amides; Antiviral Agents; Carbamates; Cobicistat; Darunavir; Dibenzothiepins; Drug Combinations; Drug Therapy, Combination; Humans; Imidazoles; Indoles; Iran; Lopinavir; Morpholines; Pyrazines; Pyridones; Pyrrolidines; Randomized Controlled Trials as Topic; Ritonavir; SARS-CoV-2; Sofosbuvir; Treatment Outcome; Triazines; Valine; COVID-19 Drug Treatment
PubMed: 34253490
DOI: 10.1016/j.jmii.2021.05.011 -
Frontiers in Immunology 2022To conduct a meta-analysis with the aim of comparing the outcomes of antiviral prophylaxis and preemptive therapy for the prevention of cytomegalovirus (CMV) infection... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To conduct a meta-analysis with the aim of comparing the outcomes of antiviral prophylaxis and preemptive therapy for the prevention of cytomegalovirus (CMV) infection in liver transplant (LT) recipients.
METHODS
We searched databases for qualified studies up until March 2022. Finally, a meta-analysis was carried out using a fixed-effect or random-effect model based on the heterogeneity.
RESULTS
With a total of 1834 LT patients, the pooled incidence of CMV infection and CMV disease in the overall LT recipients using antiviral prophylaxis and preemptive therapy were 24.7% vs. 40.4% and 6.4% vs. 9.4%, respectively. Our meta-analysis exhibited a significant reduction in the incidence of CMV infection due to antiviral prophylaxis when compared to preemptive therapy in the high-risk group (OR: 6.67, 95% CI: 1.73, 25.66; p = 0.006). In contrast, there was a significant reduction in the incidence of late-onset of CMV disease in preemptive therapy compared to antiviral prophylaxis in the high-risk group (OR: 0.29, 95% CI: 0.12, 0.74; p = 0.009). However, the incidence of CMV disease, allograft rejection, graft loss, drug related adverse effects, opportunistic infections and mortality did not differ significantly between both the interventions (all p> 0.05).
CONCLUSIONS
We found the use of antiviral prophylaxis, compared with preemptive therapy, is superior in controlling CMV infection and prolonging the time to CMV disease in LT recipients without an increased risk of opportunistic infections, allograft rejection, graft loss, drug related adverse effects, development of drug resistance, and mortality.
Topics: Humans; Cytomegalovirus; Liver Transplantation; Cytomegalovirus Infections; Drug-Related Side Effects and Adverse Reactions; Opportunistic Infections; Antiviral Agents
PubMed: 36439159
DOI: 10.3389/fimmu.2022.953210 -
International Journal of Molecular... Aug 2022Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a viral agent that causes Coronavirus disease 2019 (COVID-19), a disease that causes flu-like symptoms... (Review)
Review
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a viral agent that causes Coronavirus disease 2019 (COVID-19), a disease that causes flu-like symptoms that, when exacerbated, can have life-threatening consequences. COVID-19 has been linked to persistent symptoms, sequelae, and medical complications that can last months after the initial infection. This systematic review aims to elucidate the innate and adaptive immune mechanisms involved and identify potential characteristics of COVID-19 pathology that may increase symptom duration. We also describe he three different stages of COVID-19-viral replication, immune hyperactivation, and post-acute sequelae-as well as each phase's corresponding immune response. Finally, we use this multiphasic approach to describe different treatment approaches for each of the three stages-antivirals, immunosuppressants and monoclonal antibodies, and continued immunosuppressants-to fully curate the treatment to the stage of disease.
Topics: Antiviral Agents; Humans; Immunosuppressive Agents; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35955740
DOI: 10.3390/ijms23158606 -
Medicina Intensiva 2020On 31 December 2019, the Health Commission of Hubei Province of China first unveiled a group of unexplained cases of pneumonia, which WHO subsequently defined as the new...
On 31 December 2019, the Health Commission of Hubei Province of China first unveiled a group of unexplained cases of pneumonia, which WHO subsequently defined as the new coronavirus of 2019 (SARS-CoV-2). SARS-CoV-2 has presented rapid person-to-person transmission and is currently a global pandemic. In the largest number of cases described to date of hospitalized patients with SARS-CoV-2 disease (2019-nCoViD), 26% required care in an intensive care unit (ICU). This pandemic is causing an unprecedented mobilization of the scientific community, which has been associated with an exponentially growing number of publications in relation to it. This narrative literature review aims to gather the main contributions in the area of intensive care to date in relation to the epidemiology, clinic, diagnosis and management of 2019-nCoViD.
Topics: Age Factors; Angiotensin-Converting Enzyme 2; Antiviral Agents; Asymptomatic Infections; Betacoronavirus; COVID-19; Coronavirus Infections; Critical Care; Critical Illness; Humans; Pandemics; Peptidyl-Dipeptidase A; Personal Protective Equipment; Pneumonia, Viral; SARS-CoV-2; Standard of Care; Symptom Assessment; Triage
PubMed: 32362424
DOI: 10.1016/j.medin.2020.03.001 -
PLoS Medicine Mar 2023Current guidelines do not recommend routine antiviral prophylaxis to prevent hepatitis B virus (HBV) reactivation in non-liver solid organ transplant (SOT) recipients... (Meta-Analysis)
Meta-Analysis
Incidence, risk factors, and clinical outcomes of HBV reactivation in non-liver solid organ transplant recipients with resolved HBV infection: A systematic review and meta-analysis.
BACKGROUND
Current guidelines do not recommend routine antiviral prophylaxis to prevent hepatitis B virus (HBV) reactivation in non-liver solid organ transplant (SOT) recipients with resolved HBV infection, even in anti-hepatitis B surface antigen (anti-HBs)-negative recipients and those receiving intense immunosuppression. This systematic review and meta-analysis aimed to determine the incidence, risk factors, and clinical outcomes of HBV reactivation in non-liver SOT recipients.
METHODS AND FINDINGS
Three databases (PubMed, Embase, and Cochrane Library) were systematically searched up to December 31, 2022. Clinical studies reporting HBV reactivation in non-liver SOT recipients were included. Case reports, case series, and cohort studies with a sample size of less than 10 patients were excluded. Random-effects analysis was used for all meta-analyses. We included 2,913 non-liver SOT recipients with resolved HBV infection from 16 retrospective cohort studies in the analysis. The overall HBV reactivation rate was 2.5% (76/2,913; 95% confidence interval [95% CI 1.6%, 3.6%]; I2 = 55.0%). Higher rates of reactivation were observed in recipients with negative anti-HBs (34/421; 7.8%; 95% CI [5.2%, 10.9%]; I2 = 36.0%) by pooling 6 studies, experiencing acute rejection (13/266; 5.8%; 95% CI [2.3%, 14.5%]; I2 = 63.2%) by pooling 3 studies, receiving ABO blood type-incompatible transplantation (8/111; 7.0%; 95% CI [2.9%, 12.7%]; I2 = 0%) by pooling 3 studies, receiving rituximab (10/133; 7.3%; 95% CI [3.4%, 12.6%]; I2 = 0%) by pooling 3 studies, and receiving anti-thymocyte immunoglobulin (ATG, 25/504; 4.9%; 95% CI [2.5%, 8.1%]; I2 = 49.0%) by pooling 4 studies. Among recipients with post-transplant HBV reactivation, 11.0% (7/52; 95% CI [4.0%, 20.8%]; I2 = 0.3%) developed HBV-related hepatic failure, and 11.0% (7/52; 95% CI [4.0%, 20.8%]; I2 = 0.3%) had HBV-related death. Negative anti-HBs (crude odds ratio [OR] 5.05; 95% CI [2.83, 9.00]; p < 0.001; I2 = 0%), ABO blood type-incompatible transplantation (crude OR 2.62; 95% CI [1.05, 6.04]; p = 0.040; I2 = 0%), history of acute rejection (crude OR 2.37; 95% CI [1.13, 4.97]; p = 0.022; I2 = 0%), ATG use (crude OR 3.19; 95% CI [1.48, 6.87]; p = 0.003; I2 = 0%), and rituximab use (crude OR 3.16; 95% CI [1.24, 8.06]; p = 0.016; I2 = 0%) increased the risk of reactivation. Adjusted analyses reported similar results. Limitations include moderate heterogeneity in the meta-analyses and that most studies were conducted in kidney transplant recipients.
CONCLUSIONS
Non-liver SOT recipients with resolved HBV infection have a high risk of HBV-related hepatic failure and HBV-related death if HBV reactivation occurs. Potential risk factors for HBV reactivation include rituximab use, anti-thymocyte immunoglobulin use, anti-HBs negative status, acute rejection history, and ABO blood type-incompatible transplantation. Further research on monitoring and routine antiviral prophylaxis of non-liver SOT recipients at higher risk of HBV reactivation is required.
Topics: Humans; Hepatitis B virus; Rituximab; Retrospective Studies; Incidence; Antiviral Agents; Hepatitis B; Risk Factors; Hepatitis B Antibodies; Organ Transplantation
PubMed: 36920988
DOI: 10.1371/journal.pmed.1004196 -
The Korean Journal of Pain Oct 2021Postherpetic neuralgia (PHN) is a refractory complication of herpes zoster (HZ). To prevent PHN, various strategies have been aggressively adopted. However, the efficacy...
BACKGROUND
Postherpetic neuralgia (PHN) is a refractory complication of herpes zoster (HZ). To prevent PHN, various strategies have been aggressively adopted. However, the efficacy of these strategies remains controversial. Therefore, we aimed to estimate the relative efficacy of various strategies used in clinical practice for preventing PHN using a network meta-analysis (NMA).
METHODS
We performed a systematic and comprehensive search to identify all randomized controlled trials. The primary outcome was the incidence of PHN at 3 months after acute HZ. We performed both frequentist and Bayesian NMA and used the surface under the cumulative ranking curve (SUCRA) values to rank the interventions evaluated.
RESULTS
In total, 39 studies were included in the systematic review and NMA. According to the SUCRA value, the incidence of PHN was lower in the order of continuous epidural block with local anesthetics and steroids (EPI-LSE), antiviral agents with subcutaneous injection of local anesthetics and steroids (AV + sLS), antiviral agents with intracutaenous injection of local anesthetics and steroids (AV + iLS) at 3 months after acute HZ. EPI-LSE, AV + sLS and AV + iLS were also effective in preventing PHN at 1 month after acute HZ. And paravertebral block combined with antiviral and antiepileptic agents was effective in preventing PHN at 1, 3, and 6 months.
CONCLUSIONS
The continuous epidural block with local anesthetics and steroid, antiviral agents with intracutaneous or subcutaneous injection of local anesthetics and a steroid, and paravertebral block combined with antiviral and antiepileptic agents are effective in preventing PHN.
PubMed: 34593669
DOI: 10.3344/kjp.2021.34.4.509 -
Clinical Infectious Diseases : An... Aug 2023In a hepatitis C virus (HCV)-controlled human infection model (CHIM), healthy volunteers are inoculated with HCV and then treated. Residual hepatocellular carcinoma...
Risk of Hepatocellular Carcinoma After Spontaneous Clearance of Hepatitis C Virus and in Noncirrhosis Chronic Hepatitis C Patients With Sustained Virological Response: A Systematic Review.
In a hepatitis C virus (HCV)-controlled human infection model (CHIM), healthy volunteers are inoculated with HCV and then treated. Residual hepatocellular carcinoma (HCC) risk after viral clearance is an important consideration when evaluating the CHIM. We estimate HCC risk in spontaneously cleared HCV and in noncirrhosis after sustained virological response (SVR) to HCV treatment in a systematic review and using data from 3 cohorts: German anti-D, Taiwan, and US Veterans Affairs (VA). For noncirrhosis SVR, the overall HCC rate is 0.33 per 100 patient-years in meta-analysis. HCC rates for the German, Taiwan, and US Veterans Affairs cohorts are 0, 0.14, and 0.02 per 100 patient-years, respectively. Past hepatitis B virus exposure was not accounted for in the Taiwan cohort, while VA patients were likely tested based on liver disease/risk factors, which may confound HCC outcomes. The German cohort with no HCC after 44 years is most comparable to the CHIM participants. Although it is difficult to precisely estimate HCC risk from an HCV CHIM, the data suggest the risk to be very low or negligible.
Topics: Humans; Antiviral Agents; Carcinoma, Hepatocellular; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Liver Neoplasms; Sustained Virologic Response
PubMed: 37579210
DOI: 10.1093/cid/ciad380 -
Journal of the International AIDS... Nov 2022Globally about 1.7 million children were living with HIV in 2020. Two integrase strand transfer inhibitors, dolutegravir and raltegravir, are increasingly used in... (Review)
Review
INTRODUCTION
Globally about 1.7 million children were living with HIV in 2020. Two integrase strand transfer inhibitors, dolutegravir and raltegravir, are increasingly used in children. We conducted a systematic review to assess the effectiveness and safety of dolutegravir and raltegravir in children and adolescents living with HIV, aged 0-19 years.
METHODS
Sources included MEDLINE, Embase, the Cochrane Library, clinical trial registries, abstracts from key conferences and reference list searching. Observational studies and clinical trials published January 2009-March 2021 were eligible. Outcomes included efficacy/effectiveness (CD4 counts and viral load) and/or safety outcomes (mortality, grade 3/4 adverse events and treatment discontinuation) through 6 months or more post-treatment initiation. Risk of bias was assessed using previously published tools appropriate for the study design. Narrative syntheses were conducted.
RESULTS AND DISCUSSION
In total, 3626 abstracts and 371 papers were screened. Eleven studies, including 2330 children/adolescents, reported data on dolutegravir: one randomized controlled trial (RCT; low risk of bias), one single-arm trial (unclear risk of bias) and nine cohort studies (three low risk of bias, two unclear risk and four high risk). Ten studies, including 649 children/adolescents receiving raltegravir, were identified: one RCT (low risk of bias), one single-arm trial (low risk of bias) and eight cohort studies (four low risk of bias, three unclear risk and one high risk). Viral suppression levels in children/adolescents at 12 months were high (>70%) in most studies assessing dolutegravir (mostly second- or subsequent-line, or mixed treatment lines), and varied from 42% (5/12) to 83% (44/53) at 12 months in studies assessing raltegravir (mostly second- or subsequent-line). Across all studies assessing dolutegravir or raltegravir, grade 3/4 adverse events (clinical and/or laboratory) were reported in 0-50% of subjects, few resulted in discontinuation, few were drug related and no deaths were attributed to either drug.
CONCLUSIONS
These reassuring findings suggest that dolutegravir and raltegravir are effective and safe as preferred regimens in children and adolescents living with HIV. With the rollout of dolutegravir in paediatric populations already underway, it is critical that data are collected on safety and effectiveness in infants, children and adolescents, including on longer-term outcomes, such as weight and metabolic changes.
Topics: Child; Adolescent; Humans; Raltegravir Potassium; HIV Integrase Inhibitors; HIV Infections; Heterocyclic Compounds, 3-Ring
PubMed: 36377082
DOI: 10.1002/jia2.25970 -
The Journal of Infection May 2023The clinical impact of rapid sample-to-answer "syndromic" multiplex polymerase chain reaction (PCR) testing for respiratory viruses is not clearly established. We... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The clinical impact of rapid sample-to-answer "syndromic" multiplex polymerase chain reaction (PCR) testing for respiratory viruses is not clearly established. We performed a systematic literature review and meta-analysis to evaluate this impact for patients with possible acute respiratory tract infection in the hospital setting.
METHODS
We searched EMBASE, MEDLINE, and Cochrane databases from 2012 to present and conference proceedings from 2021 for studies comparing clinical impact outcomes between multiplex PCR testing and standard testing.
RESULTS
Twenty-seven studies with 17,321 patient encounters were included in this review. Rapid multiplex PCR testing was associated with a reduction of - 24.22 h (95% CI -28.70 to -19.74 h) in the time to results. Hospital length of stay was decreased by -0.82 days (95% CI -1.52 to -0.11 days). Among influenza positive patients, antivirals were more likely to be given (RR 1.25, 95% CI 1.06-1.48) and appropriate infection control facility use was more common with rapid multiplex PCR testing (RR 1.55, 95% CI 1.16-2.07).
CONCLUSIONS
Our systematic review and meta-analysis demonstrates a reduction in time to results and length of stay for patients overall along with improvements in appropriate antiviral and infection control management among influenza-positive patients. This evidence supports the routine use of rapid sample-to-answer multiplex PCR testing for respiratory viruses in the hospital setting.
Topics: Humans; Influenza, Human; Multiplex Polymerase Chain Reaction; Viruses; Respiratory Tract Infections; Antiviral Agents
PubMed: 36906153
DOI: 10.1016/j.jinf.2023.03.005